Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation
文献类型:期刊论文
作者 | Gao, Shan1; Xiong, Jie2,3; Zhang, Chunchao4; Berquist, Brian R.5; Yang, Rendong6; Zhao, Meng6; Molascon, Anthony J.1; Kwiatkowski, Shaina Y.1; Yuan, Dongxia2; Qin, Zhaohui6,7 |
刊名 | GENES & DEVELOPMENT |
出版日期 | 2013-08-01 |
卷号 | 27期号:15页码:1662-1679 |
ISSN号 | 0890-9369 |
关键词 | histone methyltransferase H3 Lys 27 methylation replication stress replication elongation ssDNA replication origin |
通讯作者 | Miao, W (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China. |
中文摘要 | Replication of nuclear DNA occurs in the context of chromatin and is influenced by histone modifications. In the ciliate Tetrahymena thermophila, we identified TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA replication stress, manifested by the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions, including replication origins, as hot spots for replication stress in Delta TXR1 cells. Delta TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while Delta EZL2 cells, deleting a Drosophila E(z) homolog, were deficient in H3K27 di- and trimethylation, with no detectable replication stress. A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of Delta TXR1, corroborating H3K27me1 as a key player in DNA replication. Additionally, we demonstrated interactions between TXR1 and proliferating cell nuclear antigen (PCNA). These findings support a conserved pathway through which H3K27me1 facilitates replication elongation. |
英文摘要 | Replication of nuclear DNA occurs in the context of chromatin and is influenced by histone modifications. In the ciliate Tetrahymena thermophila, we identified TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA replication stress, manifested by the accumulation of ssDNA, production of aberrant replication intermediates, and activation of robust DNA damage responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions, including replication origins, as hot spots for replication stress in Delta TXR1 cells. Delta TXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation (H3K27me1), while Delta EZL2 cells, deleting a Drosophila E(z) homolog, were deficient in H3K27 di- and trimethylation, with no detectable replication stress. A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of Delta TXR1, corroborating H3K27me1 as a key player in DNA replication. Additionally, we demonstrated interactions between TXR1 and proliferating cell nuclear antigen (PCNA). These findings support a conserved pathway through which H3K27me1 facilitates replication elongation. |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
类目[WOS] | Cell Biology ; Developmental Biology ; Genetics & Heredity |
研究领域[WOS] | Cell Biology ; Developmental Biology ; Genetics & Heredity |
关键词[WOS] | RIBOSOMAL-RNA GENES ; EUKARYOTIC DNA-REPLICATION ; NUCLEAR ANTIGEN PCNA ; SINGLE-STRANDED-DNA ; S-PHASE CHECKPOINT ; CHROMATIN-STRUCTURE ; CELL-CYCLE ; HETEROCHROMATIN FORMATION ; GENOME STABILITY ; DAMAGE RESPONSE |
资助信息 | NIH [R01-GM087343, 1P41RR018627, R01-GM53572, R01-HG005119]; National Natural Science Foundation of China [31071993]; Fund of State Key Laboratory of Genetics Resources and Evolution [GREKF10-09]; University of Michigan Rackham Graduate Student Research Grant |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000322716000005 |
公开日期 | 2014-01-06 |
源URL | [http://ir.ihb.ac.cn/handle/342005/19611] |
专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
作者单位 | 1.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA 2.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China 3.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Wuhan 430072, Peoples R China 4.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA 5.Texas A&M Hlth Sci Ctr, Coll Med, Dept Mol & Cellular Med, College Stn, TX 77843 USA 6.Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA 7.Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA 8.Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA 9.Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA |
推荐引用方式 GB/T 7714 | Gao, Shan,Xiong, Jie,Zhang, Chunchao,et al. Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation[J]. GENES & DEVELOPMENT,2013,27(15):1662-1679. |
APA | Gao, Shan.,Xiong, Jie.,Zhang, Chunchao.,Berquist, Brian R..,Yang, Rendong.,...&Liu, Yifan.(2013).Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation.GENES & DEVELOPMENT,27(15),1662-1679. |
MLA | Gao, Shan,et al."Impaired replication elongation in Tetrahymena mutants deficient in histone H3 Lys 27 monomethylation".GENES & DEVELOPMENT 27.15(2013):1662-1679. |
入库方式: OAI收割
来源:水生生物研究所
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